Concise Review: The Coming of Age of Stem Cell Treatment for Corneal Surface Damage

Abstract

The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,000 CLET procedures have been reported from around the world, with varying degrees of success. In this paper, we compare the methods of cultivation and the outcomes and discuss some problem areas, use of other cells as substitutes for limbal epithelium, and various carrier materials used in transplantation. Our analysis suggests that CLET as a treatment for corneal surface damage has come of age. We also highlight a simpler procedure (simple limbal epithelial transplantation) that involves cultivation of limbal tissue in situ on the surface of the cornea in vivo and that has outcomes comparable to CLET.

Successful management of severe unilateral chemical burns in children using simple limbal epithelial transplantation (SLET)

“…The previous reports on CLET suggest that most of stem cell transplant failures occur within first few months (8 months in the largest series (444 cases) on CLET) 28. In our study, the fourth case was followed for 12 months and had no recurrence.…”

Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High‐Risk Patients

“…Recent advances in corneal transplantation techniques with a shift from penetrating to safer lamellar procedures and wide application of limbal epithelial stem cell transplantation, have resulted in improved outcomes, and have expanded the number of cases of corneal blindness that can now be treated successfully . However, patients with severe pathologies (e.g., chemical burns, previously rejected grafts, autoimmune disease, and infections) still have a high risk of rejection and failure, often needing multiple surgeries . Corneal prostheses are available, but they remain mainly for end‐stage disease and even if implanted as primary procedure they often are accompanied by vision‐threatening complications, leaving an unmet need for a de novo solution for high‐risk patients.…”

“…2 However, patients with severe pathologies (e.g., chemical burns, previously rejected graft s, autoimmune disease, and infections) still have a high risk of rejection and failure, oft en needing multiple surgeries. [3][4][5][6][7][8] Corneal prostheses are available, but they remain mainly for end-stage disease and even if implanted as primary procedure they oft en are accompanied by visionthreatening complications, 1,9 leaving an unmet need for a de novo solution for high-risk patients.…”

Simple Limbal Epithelial Transplantation

“…7,8 Regulatory issues and the expenses of maintaining a clinical-grade laboratory limit the use of ex vivo cultivation, whereas conventional limbal grafting requires no special infrastructure, but is technically demanding and carries some risk to the donor eye. 10 No head-to-head trials have been conducted, and it is unclear whether one technique is more effective than the other. Therefore, availability of resources or individual preference, rather than scientific evidence, usually determines which technique a particular surgeon or center adopts.…”